Where an electrically conducting liquid is placed within a strong electric field, the liquid spontaneously sprays out of the tip of a capillary tube by the action of the field. This phenomenon is termed electrospray and has been known for many years. The electrospray phenomenon was applied to mass spectrometry of samples in solution form in the former half of 1980s and has come to be widely used in electrospray mass spectrometers.
Referring to FIG. 1, there is shown a conventional electrospray mass spectrometer for use with a sample source 31 for supplying a sample in solution form, e.g., a liquid chromatograph (LC) or solution tank. This solution sample (e.g., an LC mobile phase) from the sample source 31 is sent to a capillary 32 by a pump (not shown). This capillary 32 is made of a metal and has an inside diameter of 30 to 100 μm and an outside diameter of 150 to 250 μm. The sample pumped into the capillary 32 is driven by an LC pump or capillarity, sucked into the capillary 32, and reaches the tip of the capillary 32.
A high voltage of several kilovolts is applied between the capillary 32 and the counter electrode 34 of the mass spectrometer 33 to produce a strong electric field. The solution sample in the capillary 32 is electrostatically sprayed into the space between the capillary 32 and the counter electrode 34 under atmospheric pressure and disperses into the air as charged liquid droplets. At this time, the flow rate of the solution sample is 1 to 10 microliters per minute. Since the produced charged liquid droplets are clusters formed by solvent molecules collected around sample molecules, only ions of the sample molecules can be left if heat is applied to evaporate off the solvent molecules.
One method of creating sample ions from charged liquid droplets consists of heating nitrogen gas to about 70° C., supplying the hot gas into the space between the capillary 32 and the counter electrode 34, and electrostatically spraying the droplets into the space to evaporate off the solvent of the liquid droplets. Another method consists of heating a sampling orifice 35 formed in the counter electrode 34 of the mass spectrometer 33 to about 80° C. and evaporating off the solvent of the liquid droplets by the resulting radiative heat or thermal conduction. These methods are known as ion evaporation.
Sample ions created by ion evaporation are accepted into the mass spectrometer 33 through the sampling orifice 35 formed in the counter electrode 34. To introduce the sample ions under atmospheric pressure, differentially pumped walls are formed. In particular, a partition surrounded by the sampling orifice 35 and a skimmer orifice 36 is evacuated to about 200 Pa by a rotary pump (RP) (not shown). Meanwhile, a partition surrounded by the skimmer orifice 36 and a partition wall 37 is evacuated to about 1 Pa by a turbomolecular pump (TMP) (not shown). The stage located behind the partition wall 37 is evacuated to about 10−3 Pa by the TMP, and a mass analyzer 38 is placed in this stage.
A ring lens 39 is placed in a low-vacuum partition surrounded by the sampling orifice 35 and the skimmer orifice 36. A voltage that is positive or negative is applied to the ring lens 39, depending on whether the sample ions are positive or negative, respectively, to prevent diffusion of the sample ions. An ion guide 40 to which an RF voltage is applied is placed in a moderate-vacuum partition surrounded by the skimmer orifice 36 and the partition wall 37 to guide sample ions into the mass analyzer 38.
In a modern system based on the instrument shown in FIG. 1, a sheath tube (not shown in FIG. 1) through which a nebulizing gas can flow is mounted around the capillary 32, thus coping with a high flow rate of sample such as 10 to 1000 microliters/min as encountered with an LC mobile phase. In this new type of electrospray ion source, a high flow rate of solution sample more than 10 microliters/min that cannot be fully nebulized by electric field force alone can be fully nebulized by the force of the nebulizing gas.
An electrospray ion source is characterized in that it provides a very soft ionization method which utilizes neither application of high temperature nor bombardment of high-energy particles in ionizing sample molecules. Therefore, highly polar biomolecular polymers such as peptide, proteins, and nucleic acids can be readily ionized into polyvalent ions almost nondestructively. Furthermore, since they are polyvalent ions, they can be investigated with a relatively small-sized mass spectrometer even if the molecular weight is in excess of ten thousands.
In recent years, however, some examples of samples have been reported in which the molecular structure of sample ions is destroyed even if they are ionized by a very soft ionization method such as electrospray ionization. One example is a huge organic-metal complex typified by a supramolecular compound having a high degree of orderliness because of self-assembly of transition metal (such as platinum)-complex. These metal complexes are unstable against ionization provided by electrospray that is a soft ionization method, as well as against ion bombardment and heat. Consequently, during ionization, the molecular structure is destroyed.
In an attempt to solve this problem, a new type of electrospray mass spectrometer has been developed (Japanese patent laid-open No. 2000-285847). In particular, a nebulizing gas supplied into an electrospray ion source and a desolvation chamber for charged particle droplets are cooled by a refrigerant such as liquid nitrogen to minimize the heat applied to sample ions during ionization. This cooling device promotes electrolytic dissociation to form molecular ions base on increasing polarizability of the compounds and/or solvent molecules caused by the higher dielectic constant at low temperature. This method is known as coldspray ionization, and has first succeeded in accurately measuring the mass numbers of unstable self-assembling organic-metal complexes as mentioned previously by directly spraying liquid nitrogen against the desolvation chamber, as shown in FIG. 2.
Undoubtedly, the feature of such a coldspray mass spectrometer is that the nebulizing gas and desolvation chamber are cooled by a refrigerant such as liquid nitrogen to minimize the application of heat to charged liquid droplets. In the prior art instrument, however, the desolvation chamber is directly cooled by liquid nitrogen and so overcooling occurs. This makes it difficult to set the desolvation chamber to a temperature range best adapted for measurements. It takes a long time until the instrument stabilizes. Furthermore, the cooling gas for cooling the desolvation chamber directly flows into the ionization chamber, thus disturbing the air flow in the chamber. Consequently, it is difficult to stabilize the ion beam. In addition, when a measurement is being performed by the coldspray ionization method, isolation from the outside environment is not complete and so dewing occurs inside a chamber accommodating electrical circuitry. This results in electrical leakage, which in turn makes it difficult to perform stable measurements for a long time. Another problem is that it is impossible to switch the mode of operation between coldspray ionization mode and normal electrospray ionization mode.